There is limited data to assess the true risk of unprotected oral- genital contact for acquisition Of HIV infection. Animal data suggests of tonsil tissue can be easily infected with SIV and some observational studies suggest the rate of oral transmission may be as high as 20-25% among men who have sex with other men. However there are no data to estimate risk for heterosexual oral-genital contact. This 4 year proposal is for 3 inter-related studies to l) examine the attributable risk of oral-genital contact for transmission of HlV (and factors associated that may increase the risk), 2) study initial replication events in vivo, at the level of the mucosal surface, among persons with recent sexual exposure to HIV, and 3) develop an ex vivo model of oral transmission using human oropharyngeal tissues and primary isolates of HIV. The 1st study will enroll serodiscordant couples into a prospective, longitudinal 24 month follow-up study. Couples will fill out weekly sex diaries and have regular standardized dental examinations and laboratory monitoring of blood and semen to determine factors that might affect risk of oral-genital contact for HIV transmission. Analysis will be centered on number of people seroconverting by oral contact, the per contact risk, viral load in blood and semen of the source partner, epidemiologic parameters (smoking, flossing, dental appliances, etc.), and dental condition of the recipient (peridontal indicies, salivary flow rate, and mucosal integrity). The 2nd study will focus on patients referred for post sexual exposure prophylaxis (PSEP). Subjects will undergo mucosal swab and biopsy to determine duration of infectious HIV on the mucosa and in situ hybridization and immunocytochemistry to determine which cell(s) are initially infected. The 3rd study will be to develop an ex vivo model of oral transmission to allow a more controlled exploration of potential mechanisms discovered in vivo. Studies will be done to determine which seminal cells are capable of harboring productive infection and which human oropharyngeal tissues can be infected from virus produced in the seminal cells.